Tetrahydrobiopterin-free neuronal nitric oxide synthase: evidence for two identical highly anticooperative pteridine binding sites

Biochemistry
A C F GorrenB Mayer

Abstract

The properties of neuronal nitric oxide synthase containing one tetrahydrobiopterin (BH4) per dimer [nNOS(BH4+)] were compared to those of the BH4-free enzyme [nNOS(BH4-)]. The stimulation by BH4 of the formation of L-citrulline at the expense of H2O2 production unambiguously demonstrated that BH4 is essential in coupling reductive oxygen activation to Arg oxidation. The clear difference between the Stokes radii of nNOS(BH4-) and nNOS(BH4+) indicates that the introduction of one BH4 per dimer significantly changes the enzyme structure. Whereas the heme in nNOS(BH4+) was primarily high-spin, nNOS(BH4-) contained mainly low-spin heme. This was slowly converted into the high-spin form with Arg and/or BH4, with a rate that was independent of the concentration of either compound. Dithiothreitol inhibited the Arg/BH4-induced spin conversion by stabilizing low-spin heme. Formation of high-spin heme, with rates varying from 0.04 to 0.4 min-1, always correlated to an equally fast increase in activity. Radioligand binding studies showed the rapid association (within 20 s) of BH4 to nNOS(BH4-), but not to nNOS(BH4+), after preincubation with Arg. Complete and monophasic dissociation of radioligand occurred in the presence of excess unlabe...Continue Reading

References

Jan 1, 1991·Annual Review of Pharmacology and Toxicology·A J Fulco
Nov 15, 1994·The Biochemical Journal·E R WernerH Wachter
Jan 1, 1995·Annual Review of Physiology·O W Griffith, D J Stuehr
Jan 1, 1993·Annual Review of Nutrition·S Kaufman
Oct 11, 1993·FEBS Letters·K N Degtyarenko, A I Archakov

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Citations

Mar 23, 2010·Pflügers Archiv : European journal of physiology·Ulrich Förstermann
Oct 19, 1999·Brain Research. Brain Research Reviews·F TorreillesJ Torreilles
Jul 17, 1999·Biochimica Et Biophysica Acta·R E Sharp, S K Chapman
Apr 12, 2002·Progress in Neurobiology·François Torreilles, Jacques Touchon
Jan 20, 1998·Trends in Biochemical Sciences·B Mayer, B Hemmens
May 18, 2011·Journal of Chemical Information and Modeling·Nicolas FloquetJean Martinez
Nov 7, 2001·The Biochemical Journal·H YoneyamaH Kosaka
Mar 7, 2008·Antioxidants & Redox Signaling·Eberhard SchulzThomas Münzel
Aug 9, 2012·Antioxidants & Redox Signaling·Ricardo CarnicerDavid A Kass
Sep 6, 2011·European Heart Journal·Ulrich Förstermann, William C Sessa
Sep 20, 2007·Journal of Cardiovascular Pharmacology·An L Moens, David A Kass
Sep 1, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Jianzhong AnYang Shi
Dec 6, 2003·Clinical Chemistry and Laboratory Medicine : CCLM·Olaf Stanger, Martin Weger
Jul 15, 2011·Interdisciplinary Toxicology·Jana KopincováIveta Bernátová
Jun 13, 2001·Biochemical and Biophysical Research Communications·A Palumbo, M d'Ischia
Sep 7, 2000·Biochemical and Biophysical Research Communications·M ColasantiG Musci
Dec 4, 2013·Antioxidants & Redox Signaling·Jennifer K BendallMark J Crabtree
Sep 27, 2013·International Journal of Cardiology·Yahor TratsiakovichJohn Pernow
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·J Vásquez-VivarK A Pritchard
Oct 20, 2005·Dalton Transactions : an International Journal of Inorganic Chemistry·Dennis J StuehrRuss Hille
Dec 17, 2011·Journal of Inorganic Biochemistry·Zhi-Qiang WangDennis J Stuehr
May 10, 2011·Nitric Oxide : Biology and Chemistry·Mark J Crabtree, Keith M Channon
Jul 25, 2009·Free Radical Biology & Medicine·Jeannette Vásquez-Vivar
Aug 5, 2008·Free Radical Biology & Medicine·Madhumita ChatterjeeMadhu Dikshit
Oct 4, 2006·Biochimica Et Biophysica Acta·Antonius C F Gorren, Bernd Mayer
Mar 20, 2015·Free Radical Research·J KonradiA Klinke
Apr 22, 2003·Progress in Cardiovascular Diseases·Xing Li WangJian Wang
Apr 15, 2015·Vascular Pharmacology·Kayleigh Hamilton, Andrew MacKenzie
Jan 5, 2011·Journal of Inorganic Biochemistry·Jérôme Santolini
May 13, 1999·Biochimica Et Biophysica Acta·D J Stuehr

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